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Background: Low serum concentrations of vitamin A and zinc are common in tuberculosis and may have an adverse effect on host cell–mediated responses. The role of adjunctive micronutrient supplementation on treatment outcomes is uncertain. Objective: The objective was to assess the efficacy of vitamin A and zinc supplementation on sputum smear and culture conversion and time to culture detection in adults with sputum smear–positive pulmonary tuberculosis. Design: Participants attending a primary care tuberculosis clinic in Cape Town, South Africa, were randomly assigned to receive micronutrients (single dose of 200,000 IU retinyl palmitate plus 15 mg Zn/d for 8 wk) or matching placebo. Sputum was collected weekly for 8 wk for auramine staining and culture on liquid media (BACTEC MGIT 960; Becton Dickinson, Sparks, MD). Performance status, chest radiographs, and anthropometric measures were assessed at baseline and again at 8 wk. Results: The participants (n = 154) were randomly assigned to the micronutrient (n = 77) or placebo (n = 77) group. Twenty participants were HIV infected (13%), and 12 participants had an unknown HIV status (8%). No differences in time to smear or culture conversion were observed between the treatment groups by Kaplan-Meier analysis (P = 0.15 and P = 0.38, respectively; log-rank test). Log-logistic regression analysis found no significant group interaction effect in time to culture detection over the 8-wk period (P = 0.32). No significant differences in weight gain (2.3 6 3.5 compared with 2.2 6 2.4 kg, P = 0.68) or radiologic resolution were observed between the treatment groups. Conclusion: Supplementation with vitamin A and zinc did not affect treatment outcomes in participants with pulmonary tuberculosis at 8 wk. This trial was registered at controlled-trials.com as ISRCTN80852505. Am J Clin Nutr 2011;93:93–100.